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Low-toxicity pimaricin derivative as well as preparation method and application thereof

A technology of pimaricin and its derivatives, which is applied in the development and preparation of low-toxic pimaricin derivatives, which can solve the problems of strong cytotoxicity, poor water solubility, and restrictions on the development and application of polyene antibiotics, and reduce the Cytotoxicity, good antifungal activity

Pending Publication Date: 2021-11-02
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its water solubility is relatively poor and it also has strong cytotoxicity, which seriously limits the development and application of polyene antibiotics.

Method used

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  • Low-toxicity pimaricin derivative as well as preparation method and application thereof
  • Low-toxicity pimaricin derivative as well as preparation method and application thereof
  • Low-toxicity pimaricin derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Embodiment one: antifungal activity detection

[0043] A. Use Candida albicans SC5314 (ATCC MYA-2876) as the experimental standard strain. Candida albicans clinical strains (CCC-593, CCC-495, CCC-487, CCC-515, CCC-496, CCC-2260, CCC-2251, CCC-2242, CCC-2233, CCC-2224) were used as indicator bacteria.

[0044] B. Select a single colony of Candida albicans to prepare a bacterial suspension in the medium, and the final concentration of the bacterial solution is about 0.5-2.5×10 4 CFU / mL. Take 200 μL of the bacterial solution and add it to the first well of a flat-bottomed 96-well plate, and then add 100 μL of the bacterial solution to be tested to each well.

[0045] C. Add the drug to be tested or the positive control (amphotericin B) into the first well, pipette and mix in the first well, take 100 μL of the uniform suspension and add it to the second well, pipette and mix, repeat to the last well, Perform a 2-fold serial dilution and discard the excess bacterial solutio...

Embodiment 2

[0048] Example 2: Cytotoxicity detection

[0049] A. Oral epithelial cells are cultured in complete medium in vitro. After the cells adhere to the wall and grow to the full, digest and collect the cells, and resuspend the cells in the complete medium.

[0050] B. Each well of the 96-well plate was inoculated with 5×10 3 100 μL of cell suspension. Cell culture incubator (37°C, 5% CO 2 ) culture, and the cells were replaced with serum-free DMEM medium overnight when about 80% of the cells adhered to the wall.

[0051] C. Gradient half-dilution to obtain different concentrations of the drug to be tested or amphotericin B standard solution, add serum-free DMEM medium respectively, and the treatment time is 24 hours.

[0052] D. According to the instructions of the commercially available kit, CCK8 experiment was carried out to detect the inhibitory rate of the compound on oral epithelial cells.

[0053] E. There are 3 parallel experiments for each group of experiments, and each...

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Abstract

The invention relates to the technical field of microbial secondary metabolite modification and separation, and discloses a low-toxicity pimaricin derivative, the molecular formula of which is C33H49NO11 and the chemical structural formula of which is as follows: a Streptomyces chattanoogensis QZ02 strain is used as a chassis to construct a SelP protein back-filling strain, and through the processes of strain fermentation, thallus treatment, organic reagent extraction, medium-pressure reversed-phase chromatography crude separation, high performance liquid chromatography separation and the like, the low-toxicity pimaricin derivative Pima 9 is obtained. The compound developed by the invention shows lower cytotoxicity and has a better development prospect.

Description

technical field [0001] The invention relates to the technical field of transformation and separation of micro-secondary metabolites, in particular to the development, preparation method and application of a low-toxicity pitamamycin derivative. Background technique [0002] The invention relates to microbial secondary metabolism and separation technology, in particular to a derivative of Pimaricin and a preparation method thereof [0003] Systemic fungal infections, also known as invasive fungal infections (IFIs), mainly occur in some immunocompromised or immunocompromised populations, such as: cancer chemotherapy patients, patients receiving immunosuppression due to organ transplantation, severe Monitor patients, premature infants, AIDS patients, and patients with acquired immunodeficiency diseases, etc. According to statistics, more than 500,000 people die from invasive fungal infections every year, and this number continues to rise due to the lack of effective antifungal ...

Claims

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Application Information

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IPC IPC(8): C07H17/04C07H1/06A61K31/7048A61P31/10A23L3/3562C12P19/62C12N1/21C12R1/465
CPCC07H17/04C07H1/06A61P31/10C12P19/626C12N1/20C12N9/0004A23L3/3562Y02A50/30
Inventor 张立新刘光方文静许安安白林泉杰森·米克菲尔德刘雪婷朱国良李源航阿尔伯特·卡雷拉
Owner EAST CHINA UNIV OF SCI & TECH